Interdisciplinary approach to improve cancer treatments

Whether it focuses on determining why certain cancers develop drug resistance, finding a way to improve individual's immune systems or better understanding cancer cell evolution, fundamental scientific research will "stand up to cancer" with three new awards from the National Science Foundation (NSF). The awards arose through an innovative public-private partnership between NSF, Stand Up To Cancer (SU2C), the V Foundation for Cancer Research, The Lustgarten Foundation, Breast Cancer Research Foundation and Bristol-Myers Squibb.

"These research projects are quite dissimilar, but they have two things in common," said Fleming Crim, assistant director for NSF's Mathematical and Physical Sciences Directorate. "They challenge what we know and don't know about cancer at the most fundamental level, and they are attempting to tackle some of the most pressing issues in cancer treatment today."

Announced in September 2014, the partnership committed $5 million towards transformational, theoretical, biophysical approaches to cancer, with the potential for significant impact on basic science research and potentially on treatment.

"This is an example of how biology, physical sciences and mathematics can work together to address complex problems in biology," said James Olds, assistant director for NSF's Biological Sciences Directorate.

"Theoretical physics brings an important perspective to studying biological issues," said Krastan Blagoev, program director of NSF's Physics of Living System Program, who worked on building the unique public-private partnership. "Using an interdisciplinary approach to living systems helps researchers solve some basic science problems that stop us from making further progress in understanding and treating cancer."

"Stand Up To Cancer has demonstrated we can accelerate new effective cancer treatments through collaborations across institutions and research disciplines, getting researchers out of their silos," said SU2C Scientific Advisory Chairperson Phillip A. Sharp, professor at the Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology. "With these convergence teams, SU2C will advance translational cancer research beyond the long-held view that scientists 'discover,' engineers 'invent,' and entrepreneurs 'innovate.'"

In February 2015, SU2C held a workshop to follow up on the cancer partnership announcement. The workshop brought together leading clinicians and theoretical physicists to hone in on transformative approaches with the potential to catapult cancer research forward.

The three awards are:

Rational design of anticancer drug combinations with dynamic multidimensional input

Réka Albert, Penn State University; Eric Siggia, Rockefeller University; José Baselga, Memorial Sloan Kettering Cancer Center; Levi Garraway, Dana-Farber/Harvard Cancer Center; and Raul Rabadan, Columbia University

Why cancer treatments become ineffective has long confounded clinicians and is the main reason behind cancer's deadliness. This project will characterize the molecular network that causes this drug resistance. The researchers will focus on two cancers: estrogen-positive breast cancer and melanoma, the most lethal skin cancer. Using quantitative network analysis, they will work to identify networks responsible for drug resistance and explore ways to bypass that resistance at a molecular level. If successful, the theory could likely be used to improve treatments for other cancers that face drug resistance issues.

Liberating T-cell mediated immunity to pancreatic cancer

Jeffrey Drebin, University of Pennsylvania; Curtis Callan, Princeton University; David Ting, Massachusetts General Hospital and Harvard Medical School

A promising recent approach to cancer treatment is immunotherapy, which works by stimulating patients' own immune systems to fight tumor cells. Unfortunately, this approach has had little success in pancreatic cancer. Mechanisms that prevent an effective immune response include the release of immune-suppressing molecules by the tumor environment, as well as the physical barrier in the tissue preventing immune cells from reaching their target. The heart of this proposal uses theoretical modeling and statistical understanding of T-cell repertoires to design immunotherapy treatment strategies that can be tested in clinical settings.

The genetic, epigenetic and immunological underpinnings of cancer evolution through treatment

Ross Levine, Memorial Sloan Kettering Cancer Center; Daniel Fisher, Stanford University; Harlan Robins, Fred Hutchinson Cancer Research Center; Jeffrey Engelman, Massachusetts General Hospital; Steven Altschuler, University of California, San Francisco; and Chang Chan, Rutgers University

A single cancerous tumor can contain many different kinds of mutations in different cells, which affect patient prognosis: a higher degree of heterogeneity (cell variation) in a tumor corresponds to a lower survival rate. In this project, oncologists and physicists will study evolutionary dynamics leading to heterogeneity in cancer, focusing on acute myeloid leukemia and a specific type of non-small cell lung cancer. They hope to develop a quantitative framework from science-based data mining to produce more accurate survival forecasts that facilitate better treatment decisions.

Source: National Science Foundation